ความสัมพันธ์ของความผันแปรในยีน SCNIA, UGT1A4 และ ABCB1 กับการตอบสนองต่อยาลาโมทริจินในผู้ป่วยโรคลมชักชาวไทย / กรกฎ บัวเทศ = Association of variants in SCN1A, UGT1A4 and ABCB1 genes with lamotrigine responsiveness in Thai epileptic patients
Lamotrigine (LTG) is a new generation antiepileptic drug for various types of epilepsy. About 40 percent of the patients on LTG cannot achieve goal for seizure control which potentially leads to several negative consequences. Treatment response in individual patients is influenced by multiple factors including clinical factors and genetic variability. Genetic variants in genes involved in the pharmacokinetics and pharmacodynamics of LTG, may influence the drug response in patients with epilepsy. Therefore, this study aimed to investigate the association between three SNPs in SCN1A, UGT1A4 and ABCB1 genes, along with clinical factors and response to LTG treatment in Thai epileptic patients. 104 Thai patients diagnosed with epilepsy and being treated with LTG were included in the study. Two phenotypic groups were classified as LTG-responsive and LTG-resistant epilepsy. In addition to clinical data, blood samples were collected and genotyped for 3 candidate SNPs including, SCN1A IVS5N+5 G>A, UGT1A4 c.142 T>G and ABCB1 c.3435 C>T. The allele frequencies of the studied variants in Thai epileptic patients were as follows: SCN1A IVS5N+5 G>A = 61%, UGT1A4 c.142 T>G = 25% and ABCB1 c.3435 C>T = 48%. A multiple logistic regression model revealed a significant association of LTG responsiveness with ABCB1 c.3435 C>T, age at the onset of epilepsy and polytherapy. Patients with LTG resistant epilepsy were significantly more likely to have CC and CT genotypes than patients with LTG responsive epilepsy (adjusted OR = 3.95 [95% CI: 1.05-14.48] and adjusted OR = 8.07 [95% CI: 2.26-28.80], respectively). The SCN1A IVS5N+5 G>A and UGT1A4 c.142 T>G genotypes revealed no significant influence on response to LTG. In this study the pharmacogenetic model explain 40.9% of the LTG responsiveness (R² = 0.49). This study suggests that the ABCB1 c.3435 C>T polymorphism along with age at the onset of epilepsy and polytherapy may influence the response to LTG in Thai epileptic patients. This finding could lead to further study for LTG treatment optimization in individual patients, resulting in more efficacious treatment.